Ideas based on Greyhawk stuff from previous editions:
Vecna's ascension from demi-god to full blown god, ala Die Vecna Die, etc.
Actually, I had 2 ideas for a world-shaking event. They are quite drastic and, from the feedback I've received so far, unnecessary I think. But here they are:
1) A toned down copy of the FR adventure path that lead up to the Spellplague (except adapted to GH of course):
Cormyr: The Tearing of the Weave
Shadowdale: The Scourging of the Land
Anauroch: The Empire of Shade
I haven't read these so I'm not sure how successful I'd be adapting them. Perhaps instead of Shar going up against Mystra, it could be Vecna verses Boccob?
A mini Spellplague would then ensue but it would last only a few months (no 100 year time jump) and makes no major changes except to alter the flux of magic. Perhaps Boccob doesn't die but is just wounded in someway and must recover.
2) An epic adventure path following the Gord the Rogue series of books:
Artifact of Evil
Sea of Death
City of Hawks
Come Endless Darkness
Dance of Demons
Instead of Gord, though, the PCs would take centre stage. The end of this epic adventure could be joyous with the defeat or banishment of Tharizdun, or grim with Tharizdun triumphant.
If Tharizdun is triumphant, then the rest of the gods sacrifice themselves (or a great deal of their power) to imprision the Dark God on Oerth (so he cannot conquer the rest of the multiverse). This could make for an interesting setting like the Midnight campaign where evil has won.
These were the ideas I was tossing around anyway
